Chronic hepatitis B virus (HBV) continues to be an important worldwide cause of morbidity, mortality and source of potential new infections. There are estimated to be 300 million carriers of HBV in the world. Interferon alpha-2b is the only drug approved for the treatment of chronic HBV. Long term suppression of virus has only been accomplished in 25-50% of people receiving interferon. Furthermore many are unable to tolerate the drug because of side effects. Therefore effective and safe new agents for the treatment of hepatitis B infection are needed. Adefovir (PNMA or 9-[2-(phosphonomethoxy)ethyl]adenine) is a broad spectrum nucleotide analog with in vitro and in vivo activity against hepadnaviruses, retroviruses, and herpesviruses. It also has activity against duck (DHBV) and human hepatitis B (HBV) in vitro and in animal models. Adefovir dipivoxil, also known as bis-POM PMEA; is an orally available prodrug of adefovir (PMEA). In the DHBV model of infection, adefovir was found to be active in both hepatic and extrahepatic sites, such as bile ducts and the pancreas, with reductions in DHBV markers. When administered at a daily dose of 120 mg to 15 HBV-infected people for four weeks, adefovir dipivoxil was associated with rapid and significant declines in serum HBV DNA levels. Elevations in liver transaminases were noted in participants receiving active drug. After termination of dosing, HBV DNA levels returned to baseline over on to six weeks in active drug recipients. Due to the potent antiviral activity observed in this initial trial, further study of this drug in patients with chronic HBV is proposed. As part of a multicenter trial, we plan to study adefovir dipivoxil at lower doses (30, 60 mg/day) in addition to the dose previously evaluated (120 mg/day). Subjects will receive drug daily for 12 weeks in order to further evaluate the safety, tolerance and anti-HV activity of adefovir dipivoxil.